Expression of junctional adhesion molecule-A prevents spontaneous and random motility

Gianfranco Bazzoni, Paolo Tonetti, Luca Manzi, Maria R. Cera, Giovanna Balconi, Elisabetta Dejana

Research output: Contribution to journalArticlepeer-review

Abstract

Junctional adhesion molecule-A (JAM-A) is a cell-surface glycoprotein that localizes to intercellular junctions and associates with intracellular proteins via PSD95-Dlg-ZO1-binding residues. To define the functional consequences of JAM-A expression, we have produced endothelial cells from JAM-A-deficient mice. We report here that the absence of JAM-A enhanced spontaneous and random motility. In turn, the enhanced motility of JAM-A-negative cells was abrogated either on transfection of exogenous JAM-A or on treatment with inhibitors of glycogen synthase kinase-3β (GSK-3β). In addition, in JAM-A-positive cells, motility was enhanced on inactivation of protein kinase Cζ (PKCζ), which is an inhibitor of GSK-3β. Although these findings suggested that JAM-A might inhibit GSK-3β, we found that expression per se of JAM-A did not change the levels of inactive GSK-3β. Thus, JAM-A expression may regulate effectors of motility that are also downstream of the PKCζ/GSK-3β axis. In support of this view, we found that JAM-A absence increased the number of actin-containing protrusions, reduced the stability of microtubules and impaired the formation of focal adhesions. Notably, all the functional consequences of JAM-A absence were reversed either on treatment with GSK-3β inhibitors or on transfection of full-length JAM-A, but not on transfection of a JAM-A deletion mutant devoid of the PSD95-Dlg-ZO1-binding residues. Thus, by regulating cytoskeletal and adhesive structures, JAM-A expression prevents cell motility, probably in a PSD95-Dlg-ZO1-dependent manner.

Original languageEnglish
Pages (from-to)623-632
Number of pages10
JournalJournal of Cell Science
Volume118
Issue number3
DOIs
Publication statusPublished - Feb 1 2005

Keywords

  • Focal adhesions
  • Glycogen synthase kinase 3
  • Junction adhesion molecule
  • Microtubules
  • Motility
  • PDZ domains

ASJC Scopus subject areas

  • Cell Biology

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